We design and test novel therapeutic interventions for modulation of rodent autoimmune models, with the intention of innovative technology transfer to treatment of patient groups.

We develop antigen-specific vaccination protocols, such as autoantigen in adjuvants that induce regulatory T cell subsets.

We have also developed a novel cell transfer therapy based on specifically activated macrophages/microglia/monocytes. We test whether such approaches can induce short-term and long-term protection in experimental models, and define the immunological basis of the protective mechanisms. The models currently being tested include MS, Alzheimer’s disease, Rheumatoid Arthritis, Type 1 Diabetes, Stroke, Pain and Brain Tumours (Glioblastoma multiformes).

WHY DOES AUTOIMMUNITY DEVELOP IN THE FIRST PLACE?
Despite that autoimmune disease are so common, their etiology is currently unknown.

What we do know is that most autoimmune diseases are antigen (protein)-specific.

As the body’s immune system should not react to its’ own proteins, we believe that alteration of protein structures through immune processes is the critical event that leads to initiation of autoimmune diseases.

We thus focus on understanding the immunological consequences of post-translational modifications of self-antigens.

Scientific hypothesis tested: Post-translational modification of autoantigens defines their three-dimensional form as non-self.

This question relates to why autoimmune disease develops in the first place. Our hypothesis is that the immune system does what it is supposed to – attacks foreign invading microorganisms, but that during this process there is damage to cells and molecules in the vicinity. Such chemical modifications of self proteins lead to them being perceived as being non-self to the immune system, leading to breaking of immune tolerance and iniation of specific autoimmune attack. We therefore believe that autoimmune disease develops as a consequence of unwanted side-effects of a ’normal’ inflammatory process.

In order to study this phenomenon we chemically modify autoantigens known to be important in inducing autoimmune diseases – insulin and glutamic acid decarboxylase for T1DM, and MOG for MS. We use modifications that are the result of activation of macrophages and neutrophils, the cells that comprise most inflammatory cells infiltrating an inflammatory site. The modifications include oxidation, chlorination, nitrosylation and citrullination and we assess the biochemical, immunological and structural effects of these modifications on the autoantigens.